Background: Isolated systolic hypertension (ISH) is a common disease in elderly people, threatening their health. Traditional Chinese medicine (TCM) treatment or integrative treatment had advantages in improving quality of life and protecting target organs, but need to be proved by large evidence-based researches. Objective: To observe the effects of TCM treatment (Jiangya Capsule) or integrative treatment (combination of Jiangya Capsule and nimodipine) on blood pressure and vasoactive agents, and their safety in elderly ISH patients. Design, setting, participants and interventions: A multicenter, randomized, double-blind controlled trial was adopted. A total of 270 elderly ISH patients recruited from Xiyuan Hospital, and TCM Hospital and Community Health Service Centers of Yanqing County of Beijing were randomly divided into 3 groups: TCM group (Jiangya Capsule plus nimodipine simulation, 90 cases), integrative group (Jiangya Capsule plus nimodipine, 90 cases) and Western medicine (WM) group (nimodipine plus Jiangya Capsule simulation, 90 cases). They were all treated for 4 weeks. Main outcome measures: Before and after 4-week treatment, office blood pressure, 24-hour ambulatory blood pressure, serum nitric oxide (NO), and plasma endothelin-1 (ET-1), thromboxane B2 (TXB2) and 6-keto-prostaglandin 1alpha (6-keto-PGF1alpha) were detected, and safety evaluation was conducted. Results: After 4-week treatment, 5 patients in TCM group were lost to follow-up and another 5 patients were excluded, and 80 patients finished the trial; 7 patients in integrative group were lost to follow-up and another 7 patients were excluded, and 76 patients finished the trial; 2 patients in WM group were lost to follow-up and another 3 patients were excluded, and 85 patients finished the trial. After treatment, systolic blood pressure (SBP) decreased in each group (P<0.05), and integrative treatment was superior to TCM or WM treatment in decreasing SBP (P<0.05). Twenty-four hour average SBP and day average SBP decreased significantly in each group, and night average SBP decreased in integrative group, and integrative treatment was superior to TCM or WM treatment in decreasing day average SBP. Serum NO and plasma 6-keto-PGF1alpha levels were elevated and plasma ET-1 and TXB(2) levels were reduced after treatment, and integrative treatment was superior to TCM or WM treatment in reducing plasma TXB(2) level. Conclusion: TCM treatment or integrative treatment has affirmative effects and safety in treating elderly ISH patients, and integrative treatment has superiority in improving some indexes, and deserves further study.